Clinical and Cost-effectiveness of a Comprehensive geriatric assessment and management for Canadian elders with Cancer-the 5C study: a study protocol for a randomised controlled phase III trial

Martine T E Puts, Tina Hsu, Caroline Mariano, Johanne Monette, Sarah Brennenstuhl, Eric Pitters, Jack Ray, Doreen Wan-Chow-Wah, Natascha Kozlowski, Monika Krzyzanowska, Eitan Amir, Christine Elser, Raymond Jang, Anca Prica, Murray Krahn, Francois Beland, Simon Bergman, Rama Koneru, Manon Lemonde, Ewa Szumacher, Joan Zidulka, Shek Fung, Anson Li, Urban Emmenegger, Rajin Mehta, Kendra Flemming, Henriette Breunis, Shabbir M H Alibhai, Martine T E Puts, Tina Hsu, Caroline Mariano, Johanne Monette, Sarah Brennenstuhl, Eric Pitters, Jack Ray, Doreen Wan-Chow-Wah, Natascha Kozlowski, Monika Krzyzanowska, Eitan Amir, Christine Elser, Raymond Jang, Anca Prica, Murray Krahn, Francois Beland, Simon Bergman, Rama Koneru, Manon Lemonde, Ewa Szumacher, Joan Zidulka, Shek Fung, Anson Li, Urban Emmenegger, Rajin Mehta, Kendra Flemming, Henriette Breunis, Shabbir M H Alibhai

Abstract

Introduction: Geriatric assessment and management is recommended for older adults with cancer referred for chemotherapy but no randomised controlled trial has been completed of this intervention in the oncology setting.

Trial design: A two-group parallel single blind multi-centre randomised trial with a companion trial-based economic evaluation from both payer and societal perspectives with process evaluation.

Participants: A total of 350 participants aged 70+, diagnosed with a solid tumour, lymphoma or myeloma, referred for first/second line chemotherapy, who speak English/French, have an Eastern Collaborative Oncology Group Performance Status 0-2 will be recruited. All participants will be followed for 12 months.

Intervention: Geriatric assessment and management for 6 months. The control group will receive usual oncologic care. All participants will receive a monthly healthy ageing booklet for 6 months.

Objective: To study the clinical and cost-effectiveness of geriatric assessment and management in optimising outcomes compared with usual oncology care.

Randomisation: Participants will be allocated to one of the two arms in a 1:1 ratio. The randomisation will be stratified by centre and treatment intent (palliative vs other).

Outcome: Quality of life.

Secondary outcomes: (1) Cost-effectiveness, (2) functional status, (3) number of geriatric issues successfully addressed, (4) grades3-5 treatment toxicity, (5) healthcare use, (6) satisfaction, (7) cancer treatment plan modification and (8) overall survival.

Planned analysis: For the primary outcome we will use a pattern mixture model using an intent-to-treat approach (at 3, 6 and12 months). We will conduct a cost-utility analysis alongside this clinical trial. For secondary outcomes 2-4, we will use a variety of methods.

Ethics and dissemination: Our study has been approved by all required REBs. We will disseminate our findings to stakeholders locally, nationally and internationally and by publishing the findings.

Trial registration number: NCT03154671.

Keywords: comprehensive geriatric assessment; cost-effectiveness analyses; frail elderly; geriatric oncology; randomized controlled trial.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Study overview. CGA, Comprehensive Geriatric Assessment.

References

    1. Canadian Cancer Society’s Steering Committee on Cancer statistics. Canadian cancer statistics 2015. 2015.
    1. Santoni G, Angleman S, Welmer AK, et al. . Age-related variation in health status after age 60. PLoS One 2015;10:e0120077 10.1371/journal.pone.0120077
    1. Wildiers H, Heeren P, Puts M, et al. . International society of geriatric oncology consensus on geriatric assessment in older patients with cancer. J Clin Oncol 2014;32:2595–603. 10.1200/JCO.2013.54.8347
    1. Puts MTE, Tapscott B, Fitch M, et al. . A systematic review of factors influencing older adults’ decision to accept or decline cancer treatment. Cancer Treat Rev 2015;41:197–215. 10.1016/j.ctrv.2014.12.010
    1. Wan-Chow-Wah D, Monette J, Monette M, et al. . Difficulties in decision making regarding chemotherapy for older cancer patients: a census of cancer physicians. Crit Rev Oncol Hematol 2011;78:45–58. 10.1016/j.critrevonc.2010.02.010
    1. Hurria A, Wildes T, Baumgartner J, et al. . NCCN clinical practice guidelines in oncology older adult oncology. Version 1.2016: NCCN, 2016.
    1. Mohile SG, Dale W, Somerfield MR, et al. . Practical assessment and management of vulnerabilities in older patients receiving chemotherapy: ASCO guideline for geriatric oncology. J Clin Oncol 2018;36:2326–47. 10.1200/JCO.2018.78.8687
    1. Pallis AG, Fortpied C, Wedding U, et al. . EORTC elderly task force position paper: approach to the older cancer patient. Eur J Cancer 2010;46:1502–13. 10.1016/j.ejca.2010.02.022
    1. Reuben DB, et al. . Comprehensive geriatric assessment and system approaches to geriatric care : Cassel CK, Leipzig RM, Cohen HJ, Larson EB, Meier DE, Capello CF, Geriatric medicine. An evidence-based approach. 4 edn New York: Springer Verlag, 2004:195–204.
    1. Kenis C, Bron D, Libert Y, et al. . Relevance of a systematic geriatric screening and assessment in older patients with cancer: results of a prospective multicentric study. Ann Oncol 2013;24:1306–12. 10.1093/annonc/mds619
    1. Baitar A, Kenis C, Moor R, et al. . Implementation of geriatric assessment-based recommendations in older patients with cancer: a multicentre prospective study. J Geriatr Oncol 2015;6:401–10. 10.1016/j.jgo.2015.07.005
    1. Puts MT, Santos B, Hardt J, et al. . An update on a systematic review of the use of geriatric assessment for older adults in oncology. Ann Oncol 2014;25:307–15. 10.1093/annonc/mdt386
    1. Hamaker ME, Schiphorst AH, ten Bokkel Huinink D, et al. . The effect of a geriatric evaluation on treatment decisions for older cancer patients--a systematic review. Acta Oncol 2014;53:289–96. 10.3109/0284186X.2013.840741
    1. Kalsi T, Babic-Illman G, Ross PJ, et al. . The impact of comprehensive geriatric assessment interventions on tolerance to chemotherapy in older people. Br J Cancer 2015;112:1435–44. 10.1038/bjc.2015.120
    1. Deschodt M, Flamaing J, Haentjens P, et al. . Impact of geriatric consultation teams on clinical outcome in acute hospitals: a systematic review and meta-analysis. BMC Med 2013;11:48 10.1186/1741-7015-11-48
    1. Ellis G, Gardner M, Tsiachristas A, et al. . Comprehensive geriatric assessment for older adults admitted to hospital. Cochrane Database Syst Rev 2017;9:CD006211 10.1002/14651858.CD006211.pub3
    1. Puts MTE, Sattar S, Kulik M, et al. . A randomized phase II trial of geriatric assessment and management for older cancer patients. Support Care Cancer 2018;26:109–17. 10.1007/s00520-017-3820-7
    1. Katz S. Assessing self-maintenance: activities of daily living, mobility, and instrumental activities of daily living. J Am Geriatr Soc 1983;31:721–7. 10.1111/j.1532-5415.1983.tb03391.x
    1. Fillenbaum GG, Smyer MA. The development, validity, and reliability of the OARS multidimensional functional assessment questionnaire. J Gerontol 1981;36:428–34. 10.1093/geronj/36.4.428
    1. Oken MM, Creech RH, Tormey DC, et al. . Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5:649–56. 10.1097/00000421-198212000-00014
    1. Charlson ME, Pompei P, Ales KL, et al. . A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987;40:373–83. 10.1016/0021-9681(87)90171-8
    1. Hurria A, Togawa K, Mohile SG, et al. . Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol 2011;29:3457–65. 10.1200/JCO.2011.34.7625
    1. Fried LP, Tangen CM, Walston J, et al. . Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56:M146–M157. 10.1093/gerona/56.3.M146
    1. Watanabe SM, Nekolaichuk CL, Beaumont C. The Edmonton Symptom Assessment System, a proposed tool for distress screening in cancer patients: development and refinement. Psychooncology 2012;21:977–85. 10.1002/pon.1996
    1. Borson S, Scanlan J, Brush M, et al. . The mini-cog: a cognitive ’vital signs' measure for dementia screening in multi-lingual elderly. Int J Geriatr Psychiatry 2000;15:1021–7. 10.1002/1099-1166(200011)15:11<1021::AID-GPS234>;2-6
    1. Guralnik JM, Simonsick EM, Ferrucci L, et al. . A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission. J Gerontol 1994;49:M85–M94. 10.1093/geronj/49.2.M85
    1. Godin G, Shephard RJ. A simple method to assess exercise behavior in the community. Can J Appl Sport Sci 1985;10:141–6.
    1. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med 2001;16:606–13.
    1. Soubeyran P, Bellera C, Goyard J, et al. . Screening for vulnerability in older cancer patients: the ONCODAGE Prospective Multicenter Cohort Study. PLoS One 2014;9:e115060 10.1371/journal.pone.0115060
    1. Mohile SG, Velarde C, Hurria A, et al. . Geriatric assessment-guided care processes for older adults: a delphi consensus of geriatric oncology experts. J Natl Compr Canc Netw 2015;13:1120–30. 10.6004/jnccn.2015.0137
    1. Corre R, Greillier L, Le Caër H, et al. . Use of a comprehensive geriatric assessment for the management of elderly patients with advanced non-small-cell lung cancer: the phase III Randomized ESOGIA-GFPC-GECP 08-02 Study. J Clin Oncol 2016;34:1476–83. 10.1200/JCO.2015.63.5839
    1. Mody L, Miller DK, McGloin JM, et al. . Recruitment and retention of older adults in aging research. J Am Geriatr Soc 2008;56:2340–8. 10.1111/j.1532-5415.2008.02015.x
    1. Grudniewicz A, Kealy R, Rodseth RN, et al. . What is the effectiveness of printed educational materials on primary care physician knowledge, behaviour, and patient outcomes: a systematic review and meta-analyses. Implement Sci 2015;10:164 10.1186/s13012-015-0347-5
    1. Cesari M, Vellas B, Hsu FC, et al. . A physical activity intervention to treat the frailty syndrome in older persons-results from the LIFE-P study. J Gerontol A Biol Sci Med Sci 2015;70:216–22. 10.1093/gerona/glu099
    1. Sink KM, Espeland MA, Castro CM, et al. . Effect of a 24-month physical activity intervention vs health education on cognitive outcomes in sedentary older adults: the LIFE randomized trial. JAMA 2015;314:781–90. 10.1001/jama.2015.9617
    1. Aaronson NK, Ahmedzai S, Bergman B, et al. . The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993;85:365–76. 10.1093/jnci/85.5.365
    1. Hurria A, Dale W, Mooney M, et al. . Designing therapeutic clinical trials for older and frail adults with cancer: U13 conference recommendations. J Clin Oncol 2014;32:2587–94. 10.1200/JCO.2013.55.0418
    1. Puts MT, Tapscott B, Fitch M, et al. . A systematic review of factors influencing older adults' decision to accept or decline cancer treatment. Cancer Treat Rev 2015;41:197–215. 10.1016/j.ctrv.2014.12.010
    1. Wildiers H, Mauer M, Pallis A, et al. . End points and trial design in geriatric oncology research: a joint European organisation for research and treatment of cancer--Alliance for Clinical Trials in Oncology--International Society Of Geriatric Oncology position article. J Clin Oncol 2013;31:3711–8. 10.1200/JCO.2013.49.6125
    1. Ramsey SD, Willke RJ, Glick H, et al. . Cost-effectiveness analysis alongside clinical trials II-An ISPOR Good Research Practices Task Force report. Value Health 2015;18:161–72. 10.1016/j.jval.2015.02.001
    1. EuroQol Research Foundation. About EQ-5D, 2016.
    1. Goossens ME, Rutten-van Mölken MP, Vlaeyen JW, et al. . The cost diary: a method to measure direct and indirect costs in cost-effectiveness research. J Clin Epidemiol 2000;53:688–95.
    1. Alibhai SM, Santa Mina D, Ritvo P, et al. . A phase II RCT and economic analysis of three exercise delivery methods in men with prostate cancer on androgen deprivation therapy. BMC Cancer 2015;15:312 10.1186/s12885-015-1316-8
    1. U.S. Department of Health and Human Services NIoHNCI. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0, 2010.
    1. Osoba D, Rodrigues G, Myles J, et al. . Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol 1998;16:139–44. 10.1200/JCO.1998.16.1.139
    1. Glick HA. Sample size and power for cost-effectiveness analysis (part 1). Pharmacoeconomics 2011;29:189–98. 10.2165/11585070-000000000-00000
    1. Muthén B, Asparouhov T, Hunter AM, et al. . Growth modeling with nonignorable dropout: alternative analyses of the STAR*D antidepressant trial. Psychol Methods 2011;16:17–33. 10.1037/a0022634
    1. Bollen K, Curran P. Latent curve models: a structural equation perspective. New Jersey: John Wiley & Sons, 2006.
    1. Willan AR, Briggs AM. Statistical analysis of cost effectiveness data. Chichester, England: John Wiley & Sons, 2006.
    1. Leggett LE, Khadaroo RG, Holroyd-Leduc J, et al. . Measuring resource utilization: a systematic review of validated self-reported questionnaires. Medicine 2016;95:e2759 10.1097/MD.0000000000002759
    1. Krahn MD, Zagorski B, Laporte A, et al. . Healthcare costs associated with prostate cancer: estimates from a population-based study. BJU Int 2010;105:338–46. 10.1111/j.1464-410X.2009.08758.x
    1. Krol M, Brouwer W, Rutten F. Productivity costs in economic evaluations: past, present, future. Pharmacoeconomics 2013;31:537–49. 10.1007/s40273-013-0056-3
    1. van Reenen M, Janssen B. EQ-5D-5L User Guide. Basic information on how to use the EQ-5D-5L instrument. Euroqol. 2015.
    1. Hughes D, Charles J, Dawoud D, et al. . Conducting economic evaluations alongside randomised trials: current methodological issues and novel approaches. Pharmacoeconomics 2016;34:447–61. 10.1007/s40273-015-0371-y
    1. Willan AR, Lin DY, Manca A. Regression methods for cost-effectiveness analysis with censored data. Stat Med 2005;24:131–45. 10.1002/sim.1794
    1. Husereau D, Drummond M, Petrou S, et al. . Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. Int J Technol Assess Health Care 2013;29:117–22. 10.1017/S0266462313000160
    1. Tango T. On the repeated measures designs and sample sizes for randomized controlled trials. Biostatistics 2016;17:334–49. 10.1093/biostatistics/kxv047
    1. Moore GF, Audrey S, Barker M, et al. . Process evaluation of complex interventions: Medical Research Council guidance. BMJ 2015;350:h1258 10.1136/bmj.h1258
    1. Guest G, Bunce A, Jonhson L. How many interviews are enough? An experiment in data saturation and variability. Field Methods 2006;18:59–82.
    1. Elo S, Kyngäs H. The qualitative content analysis process. J Adv Nurs 2008;62:107–15. 10.1111/j.1365-2648.2007.04569.x
    1. Puts MTE, Sattar S, Fossat T, et al. . The Senior Toronto Oncology Panel (STOP) Study: Research Participation for Older Adults With Cancer and Caregivers. J Natl Compr Canc Netw 2017;15:1208–15. 10.6004/jnccn.2017.0159
    1. Pallis AG, Ring A, Fortpied C, et al. . EORTC workshop on clinical trial methodology in older individuals with a diagnosis of solid tumors. Ann Oncol 2011;22:1922–6. 10.1093/annonc/mdq687

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel